5-fluorouracil (5-FU) is one of the most important chemotherapeutics in cancer treatment. It is commonly used in various chemotherapy regimens for colorectal, stomach, breast and pancreatic cancers. For example, 5-FU alone or in combination regimens such as FOLFOX and FOFIRI is the standard first line therapy in metastatic colorectal cancer. However, 5-FU is frequently associated with severe adverse effects including myelosuppression, mucositis, dermatitis, diarrhea, cardiac toxicity and even death. These adverse effects are caused at least in part by the current approach to dose determination for individual patients. The current standard of care for dosing—Body Surface Area (BSA)—only takes into account a patient's height and weight. BSA does not account for many of the factors that impact 5-FU metabolism and efficacy such as genotype, age, gender, disease state, drug-drug interactions, organ function, and comorbidities. It is therefore not so surprising that blood concentrations of 5-FU in different patients can vary by more than ten fold despite BSA-based equal dose administration.
Recent academic studies have shown that individual 5-FU dose adjustment based on pharmacokinetic monitoring of plasma 5-FU concentrations can result in significantly improved objective response rate to 5-FU. See e.g., Gemelin et al. J. Clin. Oncol., 26(13):2099-2105 (2008); Climente-Marti et al., J. Pharmaceut. Sci., 92(6):1155-1165 (2003); Milano et al., Int. J. Cancer, 41:537-541 (1988). These studies suggest that clinical testing of 5-FU blood concentrations in individual patients undergoing 5-FU therapy is clearly desirable for the purpose of 5-FU dose adjustment, optimization of therapeutic effect, and reduction of severe adverse reactions.